Exposure to high levels of air pollution clearly contributes to increased morbidity and mortality. The statistical association of these health effects is especially well correlated with exposure to high levels of particulate material with a mean aerodynamic diameter less than 2.5 ?m (PM2.5). Although the sources that contribute to this fraction depend on the local environment, most of these particles are combustion products. In urban areas, diesel exhaust particles (DEP) are often a major constituent of this regulated pollutant. For this reason, the biological responses to diesel exhaust and DEP have been extensively studied. DEP clearly induce pulmonary inflammation in controlled human exposure studies and animal models, at least partly through increased expression of neutrophil chemattractant molecules. Preliminary studies indicate that the human chemokine IL-8 and the rodent chemokine MIP-2 associate with DEP and that the associated chemokine is biologically active. The working hypotheses for this proposal are that this novel association (a) concentrates the chemokine resulting in increased localized activation of neutrophils and (b) prolongs the half-life of the chemokine in the lung resulting in a sustained inflammatory response. The specific aims of this proposal are first, to define the mechanisms of this association and second, to determine how the association affects the biological response to the chemokine. Defining the mechanisms of the association will be approached through chemical and physical analyses of the DEP characteristics that contribute to the binding, and analyses of the association and release kinetics. Analysis of the biological effects of the association will utilize in vitro and in vivo assays of the inflammatory responses to the chemokines, the DEP, and the DEP-chemokine complex. These studies will complement ongoing studies in other laboratories, which focus on the mechanisms for DEP-induced chemokine production, by characterizing this innovative mechanism by which these particles might potentiate the inflammatory responses to the chemokines. [unreadable] [unreadable] [unreadable]